A CD4 cell count below 200 cells/mm3 is associated with an increased risk of infection-related non-AIDS-defining cancers in patients taking antiretroviral therapy, Dutch investigators report in the June 15 edition of Clinical Infectious Diseases.
Older age and certain viral co-infections also increased the risk.
The investigators believe that their findings support the prompt initiation of antiretroviral therapy, and that cancer screening should be included in routine HIV care.
“Current guidelines recommend starting cART [combination antiretroviral therapy] at CD4+ cell counts which are higher than the levels of immunodeficiency that we found to be associated with an increased risk of developing malignancies, which might help in preventing malignancies in such patients,” comment the authors.
“Screening for anal human papilloma virus infections and premalignant lesions, counselling patients to quit smoking, and vaccinating against HBV [hepatitis B virus] could…reduce the incidence of non-AIDS-defining malignancies in the HIV-1 infected population treated with cART.”
Effective antiretroviral therapy means that many HIV-positive patients now have a near-normal prognosis. However, an accumulating body of research has shown that even with this treatment, individuals with HIV have an increased risk of developing some non-AIDS-related cancers.
The exact reasons for this are uncertain, but risk factors appear to include HIV-related issues such as viral load and immune suppression; smoking; and viral co-infections such as anal, cervical and oral human papilloma virus, hepatitis B and/or hepatitis C, and Epstein-Bar virus.
Investigators from the Dutch ATHENA cohort therefore designed a study to explore the role of various HIV-related and infection-related risk factors in the development of non-AIDS-defining cancers in patients taking antiretroviral therapy.
Their study sample involved 11,459 patients who started combination HIV therapy after 1996. Patients were followed until early 2009, and the median duration of follow-up per patient was 4.8 years.
Traditional risk factors for cancer were common. Most of the patients (74%) had a history of smoking and alcohol abuse was reported in 7% of individuals.
Prevalence of infections related with cancers was also high. Rates of hepatitis B and hepatitis C infection were 5% and 6% respectively.
A total of 236 non-AIDS-defining cancers were diagnosed, 43% of which were related to infections.
These included 37 cases of anal cancer, 24 head and neck cancers, 16 diagnoses of liver cancer, 24 cases of Hodgkin’s lymphoma, one case of gastric cancer, and four individuals developed cancer of the vulva.
Common non-infection-related malignancies included lung cancer (44 cases), pancreatic cancer (five instances), renal cancer (four diagnoses), bladder cancer (six cases), and testicular cancer (eight cases).
Risk factors for the more common cancers were examined in detail.
Nearly all the patients (35) who developed anal cancer were men, and 27 reported sex with another man. Longer duration with a CD4 cell count below 200 cells/mm3 (hazard ratio [HR], 1.52; 95% CI, 1.24-1.87 for every additional year), and a CD4 cell count between 200-350 cells/mm3 (HR = 1.29; 95% CI, 1.02-1.62) were significant risk factors for anal cancer.
Other risks included older age (HR for each ten-year increase, 1.35; 95% CI, 1.07-14.70), and an AIDS diagnosis before the initiation of HIV therapy (HR, 2.02; 95% CI, 1.06-3.83).
All the patients with liver cancer were men, and eight were co-infected with hepatitis B and three with hepatitis C.
The strongest risk factor for this malignancy was co-infection with hepatitis B virus (HR, 26.6; 95% CI, 9.7-72.99). Other risk factors included older age (HR, 2.06; 95% CI, 1.32-3.23), alcohol abuse (HR, 4.0; 95% CI, 1.12-14.30). Co-infection with hepatitis C virus was not significant.
Older age was a significant risk factor for lung cancer (HR per each additional decade, 2.0; 95% CI, 1.61-2.50), but surprisingly, smoking fell just short of statistical significance (HR, 7.34; 95% CI, 0.96-55.90).
Further analysis showed that severe immune deficiency increased the overall risk of non-AIDS-defining cancers (each additional year of a CD4 cell count below 200 cells/mm3, HR, 1.12; 95% CI, 1.03-1.22).
The was also trend close to statistical significance for longer duration with a CD4 count below 350 cells/mm3 (HR, 1.08; 95% CI, 0.99-1.18).
Other risk factors included chronic hepatitis B infection (HR, 1.77; 95% CI, 1.08-2.91), older age (each additional decade, HR, 1.79; 95% CI, 1.57-2.04), and an AIDS diagnosis prior to HIV therapy (HR, 1.35; 95% CI, 1.16-2.45).
Stratified analysis was then performed to see the risk factors for infection-related and non-infection-related cancers.
This showed that each year with CD4 cell count below 200 cells/mm3 increased the risk of infection-related cancers by 16% (HR, 1.16; 95% CI, 1.03-1.31).
“The risk of these malignancies is increased in immunocompromised patients, possibly because of decreased immune surveillance for oncogenic (viral) infections, as well as the presence of cancerous or pre-cancerous cells themselves,” suggest the investigators.
However, there was no relationship between immune deficiency and an increased risk of non-infection-related cancers.
The investigators conclude, “cumulative exposure to CD4+ cell counts < 200 cells/mm3 during cART was associated with an increased risk of infection-related non-AIDS-defining malignancies.”
Kesselring A et al. Immunodeficiency as a risk factor for non-AIDS-defining malignancies in HIV-1-infected patients receiving combination antiretroviral therapy. Clin Infect Dis 52: 1458-65, 2011 (click here for the free article).